1. Field of the Invention
The present invention relates to an aqueous dispersion of enteric cellulose derivatives without ester-bonded substituents, of which anionic functional groups form salts with cations. The aqueous dispersion of the present invention, which can be used as coating agents for foods and pharmaceuticals, has high dispersion stability such as high mechanical stability and high storage stability. Also, the present invention relates to a method for producing the above aqueous dispersion.
2. Description of the Related Art
Various polymers having anionic functional groups are widely used in the field of fibers and textiles, paper making, foods, feed, cosmetics, pharmaceuticals and agricultural chemicals, painting, housing materials, oil mining, ceramics, and the like. They are especially useful as an enteric material for coating use in the field of pharmaceuticals.
For pharmaceutical use, coating agents in an organic solvent phase are gradually being replaced by those in an aqueous phase, because of the remaining organic solvent in pharmaceuticals, high cost of organic solvents and unfavorable working conditions. Several known coating methods in the aqueous phase are listed as follows:
1) A method wherein polymers are dissolved in an aqueous liquid medium. PA1 2) A method wherein fine particles of water-insoluble polymers are dispersed in water. PA1 3) A method wherein latex-type aqueous dispersions of polymers are used. PA1 i) dissolving enteric cellulose derivatives without ester-bonded substituents in an organic solvent which is substantially water immiscible, PA1 ii) dispersing the solution with water in the presence of alkalies to form nontoxic salts with the anionic functional groups of the cellulose derivatives, and PA1 iii) removing the organic solvent from the dispersion.
With method 1), it is well known that the water-soluble polymers like hydroxypropyl methyl cellulose are dissolved in purified water, then the solution is applied as a film coating so as to mask the taste of medicines and improve the impact-strength of pharmaceuticals. With method 2), it is suggested that the fine particles of carboxymethyl ethyl cellulose or hydroxypropyl methyl cellulose phthalate are directly dispersed in water (U.S. Pat. No. 4,287,221). Also, it is suggested that the fine particles of carboxymethyl ethyl cellulose are dispersed in alcohol aqueous solutions with plasticizers, surfactants, emulsifiers and the like (U.S. Pat. No. 4,606,771). It is also suggested that the fine particles of carboxymethyl ethyl cellulose are dispersed in water and 0.5-15% of the cellulose are neutralized, and then the resulting products are applied as a film coating (Japanese Patent laid-open No. 59-193832).
With method 3) where the latex-type aqueous dispersion of enteric acrylic copolymers is used, it is known that various monomers having carboxyl groups are polymerized by the method of emulsion polymerization, then the polymeric dispersion is applied as a film coating. (British Patent No. 1,393,374). Also, it is known that dried acrylic enteric latex particles having functional groups capable of forming salts can be dispersed in water with agents which can form salts, and then the dispersion can be applied as a film coating. With method 3) where the latex-type aqueous dispersion of the polymers other than acrylic copolymers is used, it is suggested that the cellulose polymers can be dispersed to form the latex by the emulsion-solvent evaporation method (U.S. Pat. No. 4,177,177). Also, it is suggested that the latex of cellulose acetate phthalate made by this method is spray dried with re-dispersion agents to get the enteric film agent having improved storage stability.
However, in method 1), necessary properties like enteric properties cannot be obtained because the polymers must be dissolved in water or aqueous medium. In method 2), the suspension must be stirred continuously because of low suspension stability. Also, its film-forming property is not satisfactory because the size of the particles is large and their shape is irregular.
In the latex type aqueous dispersion of the enteric polymers which are based on the acrylic copolymers, it is difficult to completely remove the remaining monomers. Also, the dispersion is likely to change in quality according to the temperature and the shearing stress placed on it, because of properties of acrylic copolymers. Such properties are not desirable when the dispersion is used as a film coating material for pharmaceutical products. Other than the acrylic copolymers, cellulose acetate phthalate can be used to produce the latex, however, it is not an appropriate material for the aqueous dispersion because of its hydrolytic tendencies and poor storage stability. Other enteric coating agents which have ester-bonded substituents such as hydroxypropyl methyl cellulose phthalate, also exhibit poor storage stability.
Therefore, an object of the present invention is to provide an aqueous dispersion of enteric polymers, which has high dispersion stability such as high mechanical stability and high storage stability due to the dispersed particles having self-emulsion properties.
Another object is to provide a novel method for preparing the aqueous dispersion which has the above properties.
These and other objects of the invention as well as the advantages thereof can be had by reference to the following description and claims.